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Water Transport in Aquaporins: Osmotic Permeability Matrix Analysis of Molecular Dynamics Simulations

Masanori Hashido ^*, Akinori Kidera ^*  and Mitsunori Ikeguchi ^*

^* International Graduate School of Arts and Sciences, Yokohama City University, Suehiro-cho, Tsurumi-ku, Yokohama, Japan; and Institute for Molecular Science, Okazaki, Japan

Correspondence: Address reprint requests to M. Ikeguchi, E-mail: ike{at}tsurumi.yokohama-cu.ac.jp.

Single-channel osmotic water permeability (p_f) is a key quantity for investigating the transport capability of the water channel protein, aquaporin. However, the direct connection between the single scalar quantity p_f and the channel structure remains unclear. In this study, based on molecular dynamics simulations, we propose a p_f-matrix method, in which p_f is decomposed into contributions from each local region of the channel. Diagonal elements of the p_f matrix are equivalent to the local permeability at each region of the channel, and off-diagonal elements represent correlated motions of water molecules in different regions. Averaging both diagonal and off-diagonal elements of the p_f matrix recovers p_f for the entire channel; this implies that correlated motions between distantly-separated water molecules, as well as adjacent water molecules, influence the osmotic permeability. The p_f matrices from molecular dynamics simulations of five aquaporins (AQP0, AQP1, AQP4, AqpZ, and GlpF) indicated that the reduction in the water correlation across the Asn-Pro-Ala region, and the small local permeability around the ar/R region, characterize the transport efficiency of water. These structural determinants in water permeation were confirmed in molecular dynamics simulations of three mutants of AqpZ, which mimic AQP1.